米诺环素对神经病理性疼痛大鼠脊髓星形胶质细胞激活的影响

目的观察米诺环素对CCI大鼠脊髓水平GFAP表达,探讨脊髓星形胶质细胞在神经病理性疼痛中的不同时程作用。方法将110只SD大鼠随机分成5组:A组:对照组(n=15)、B组:假手术组(n=25)、C组:CCI对照组(n=25)、D组:CCI预给药组(n=25)、E组:CCI治疗组(n=25)。分别测定各组在手术前(以第0天表示)以及手术后第1、4、7、11、14天损伤侧后肢50%机械刺激缩足阈值,然后相应分别取每组大鼠L4-6段脊髓,采用免疫组化染色方法测定脊髓背角星形胶质细胞GFAP表达变化情况。结果①坐骨神经结扎后大鼠出现痛觉过敏且持续增强存在。②B组和D组亦可见星形胶质细胞有轻微的激活,C组脊髓背角星形胶质细胞在术后7d发生明显激活,至术后14d星形胶质细胞被强烈的激活;E组星形胶质细胞术后有较明显的激活但无高峰期。结论脊髓水平星形胶质细胞的激活可能对神经病理性疼痛的产生维持发挥重要作用;米诺环素术前给药抑制星形胶质细胞的激活,减轻神经病理性疼痛。     

叶酸对脑梗死大鼠星形胶质细胞GFAP表达的影响

目的:探讨叶酸对脑梗死大鼠星形胶质细胞纤维酸性蛋白(GFAP)表达的影响。方法:将SD大鼠随机分为假手术(SO)组、缺血(IM)组、缺血 低剂量叶酸(IM LFA)组和缺血 高剂量叶酸(IM HFA)组。通过叶酸灌胃给药28d后制备大脑中动脉栓塞模型,采用免疫荧光双标记的方法检测各组大鼠脑缺血后脑组织GFAP的荧光强度及BrdU GFAP双标阳性细胞密度。结果:在7d及14d4组均可见BrdU GFAP双标阳性星形胶质细胞,缺血 叶酸组GFAP荧光强度及BrdU GFAP双标阳性细胞密度均高于IM组及SO组,差异均有统计学意义(P<0.05或P<0.01)。结论:补充叶酸可以使星形胶质细胞GFAP表达增强,并促进神经干细胞的分化,从而对脑梗死大鼠具有保护作用。     

三七三醇皂苷对糖尿病大鼠学习记忆能力及星形胶质细胞活性的影响

目的 探讨三七三醇皂苷(PTS)对糖尿病大鼠学习记忆的改善作用,并从星形胶质细胞角度揭示其机制。方法 24只SD大鼠随机分为对照组、糖尿病组及PTS治疗组,每组8只。于SD大鼠腹腔注射链脲佐菌素诱导糖尿病模型,对照组为正常SD大鼠,PTS治疗组为糖尿病大鼠给予PTS治疗。检测大鼠血糖和体质量,3个月后,水迷宫实验观察各组大鼠的学习记忆功能,免疫组化染色检测脑海马区星形胶质细胞形态,Western blot法检测神经胶质纤维酸性蛋白(GFAP)及胶质细胞源性神经营养因子(GDNF)表达。结果 糖尿病组较对照组学习记忆能力减退,脑海马区星形胶质细胞胞体萎缩、突起变细,脑海马区GFAP及GDNF表达明显减少(均P<0.05)。PTS组较糖尿病组学习记忆能力改善,脑海马区星形胶质细胞形态改善、GFAP及GDNF表达明显恢复(均P<0.05)。结论 PTS能恢复糖尿病大鼠脑海马区星形胶质细胞活性,恢复GDNF表达,提高糖尿病大鼠学习记忆功能。     

IL-36Ra抑制炎性痛小鼠脊髓A1型星形胶质细胞极化

目的评价不同剂量IL-36Ra对炎性痛小鼠痛行为以及脊髓A1型星形胶质细胞极化的影响。方法雄性C57BL/6小鼠32只,采用足底注射完全弗氏佐剂(CFA)建立炎性痛模型。随机将小鼠分为CFA+生理盐水组、CFA+IL-36Ra 50 ng组、CFA+IL-36Ra 100 ng组以及CFA+IL-36Ra 200 ng组,每组8只。各组小鼠在造模后d 1~d 7,每日1次鞘内给药。同时,分别在造模前以及造模后d 1、3、5、7检测4组小鼠机械刺激缩足阈值(mechanical withdraw threshold, MWT)和辐射热刺激缩爪潜伏期(PWL)的变化。以逆转录聚合酶链反应检测IL-36Ra对CFA小鼠脊髓A1、A2型星形胶质细胞标志物表达水平的影响。以免疫组化法检测各组小鼠脊髓背角A1型星形胶质细胞标志物C3与GFAP共表达水平的变化。结果炎性痛小鼠造模后患侧MWT、PWL均明显下降,IL-36Ra(100、200 ng)可显著改善小鼠的机械性痛觉超敏与热痛觉过敏;且在治疗7 d后,IL-36Ra可降低CFA小鼠脊髓星形胶质细胞激活标志物GFAP、Lcn2的表达水平,抑制星形胶质细胞激活;同时,IL-36Ra(100、200 ng)可下调CFA小鼠脊髓A1型星形胶质细胞标志物Serping1、 H2-T23的mRNA水平,但IL-36Ra各个剂量对A2型星形胶质细胞标志物表达没有明显作用;此外,IL-36Ra还可抑制脊髓背角A1型星形胶质细胞标志物C3表达。结论 IL-36Ra可能通过抑制CFA小鼠脊髓A1型星形胶质细胞极化,进而改善小鼠炎性痛痛行为。     

严重烫伤早期脑内星形胶质细胞与GFAP表达的变化

目的:探讨星形胶质细胞形态变化及胶质原纤维酸性蛋白(GFAP)表达与严重烫伤引起的血脑屏障损伤之间的关系.方法:健康SD大鼠,随机分为正常组、烫伤组(分3、6、12、24、48 h 5个时相点),用透射电镜观察血脑屏障超微结构变化;紫外分光光度计检测脑伊文蓝(Evan's Blue,EB)含量.免疫组化观察脑GFAP表达.结果:正常组星形胶质细胞结构清楚,各种细胞器完整.烫伤后3 h线粒体肿胀,空泡化.严重烫伤后脑EB明显高于正常组(P<0.01),以6～12 h最为明显,24 h后开始下降.GFAP的阳性表达定位于星形胶质细胞的胞浆及突起内,呈棕褐色或棕黄色.GFAP阳性细胞轮廓清楚,细胞突起成星形.烫伤后GFAP阳性细胞数目明显增多,染色增强,平均光密度增高(P<0.01),12～24 h达高峰且形态不规则,48 h后开始下降.结论:严重烫伤后星形胶质细胞活化、GFAP表达增加与血脑屏障通透性增高有关,提示GFAP在严重烫伤早期对血脑屏障的损伤有重要作用.     

地佐辛减轻CCI大鼠神经病理性疼痛的实验研究

目的 通过建立坐骨神经慢性压迫性疼痛(Chronic constriction injury,CCI)模型大鼠,观察腹腔注射地佐辛的镇痛作用及其可能机制.方法 SD大鼠32只,随机分为假手术(Sham)组、模型(Model)组、地佐辛 2.5mg·kg-1(D1)组和地佐辛10mg·kg-1(D2)组等4组,每组8只,各组于手术后即刻至术后7天,每天腹腔注射1次药物,假手术组和模型组给予等体积的生理盐水.造模前和造模后1、3、5、7d观察各组大鼠的机械痛阈变化,于造模后7d免疫荧光组织化学法观测各组脊髓胶质纤维酸性蛋白(Glial Fibrillary Acidic Protein,GFAP)表达.结果 大鼠建模1天后,PWT显示CCI大鼠的机械痛阈均出现明显下降,模型组在3d时降到最低,地佐辛干预的D1组在3d对CCI大鼠的痛阈有所改善(P<0.05),随后改变不大,D2组对大鼠的痛阈有明显改善,在5d时提高最为明显(P<0.01),同时,可见7d时各组脊髓GFAP的表达有所区别,模型组GFAP的表达明显增强,D1组较模型组表达减弱(WTBXP<0.05),D2组较模型组差异有显著的统计学意义(P<0.01).结论 地佐辛对神经病理性疼痛的抑制作用可能与下调脊髓GFAP的表达,影响星形胶质细胞的活化有密切关联.     

脊髓背角星形胶质细胞Cx43组成的半通道在大鼠急性切口痛中的作用

目的 研究脊髓背角星形胶质细胞Cx43半通道在大鼠急性切口痛中的作用。方法 成年雄性SD大鼠60只,随机分为对照组(C组)、切口痛组(I组)和Gap19组。Western blot分别检测大鼠急性切口痛术后脊髓背角的Cx43及星形胶质细胞GFAP的表达变化;术前30 min,鞘内应用Gap19测定术后大鼠50%机械缩足阈值(PWT)的变化,免疫荧光检测大鼠脊髓背角的Cx43及GFAP表达的变化,ELISA检测炎症因子的变化。结果 与C组相比,I组大鼠脊髓背角Cx43和GFAP表达在术后6 h明显增加,术后3 d和7 d无改变。I组和Gap19组大鼠在切口建立后2 h、6 h、24 h、3 d的PWT明显降低(P<0.01),术后7 d无变化。与I组比,Gap19组PWT在术后2、6、24 h明显增加(P<0.01),3 d和7 d无变化。免疫荧光结果显示,I组术后6 h脊髓GFAP和Cx43表达相较C组增加(P<0.01);与I相比,Gap19组GFAP和Cx43表达明显下降(P<0.05),但术后7 d各组间无统计学差异。ELISA显示,与C组相比,I组脊髓背...     

丁苯酞增强脑缺血耐受的实验研究

目的:观察局灶性脑缺血预处理对胶质纤维酸性蛋白(GFAP)、碱性成纤维细胞生长因子(bFGF)表达的影响以及给予丁苯酞干预治疗后地变化.方法:利用二次线栓法建立局灶性SD大鼠脑缺血耐受的动物模型.(1)MCAO组:假手术 缺血组(SS MCAO);(2)IP组:预缺血 缺血组(IP MCAO);(3)给药组:预缺血 丁苯酞 缺血(IP NBP MCAO).运用对SD大鼠脑梗死体积的测定、光镜及电镜下组织病理改变及免疫组织化学染色和图像分析比较各组GFAP、bFGF的表达变化.结果:(1)IP组和给药组脑梗死体积较MCAO组减少,且给药组在3组中减少最为明显,3组闻差异有统计学意义.MCA0组超微结构损伤最严重,IP组超微结构改变明显轻于MCAO组;给药组损伤较前2组均减轻.(2)3组GFAP均有不同程度的表达,其中在给药组两者表达相对明显,且伴有星形胶质细胞形态学的改变.GFAP阳性细胞数其IOD值三者之间差异有统计学意义(P＜0.05).(3)3组bFGF分布及数量上均有不同程度的表达.其中在给药组表达最明显,3组差异有统计学意义(P＜0.05).结论:缺血预处理能够提供脑保护,诱导脑缺血耐受的形成.其可能的机制之一是通过促进星形胶质细胞的活化,启动内源性的神经营养因子-bFGF表达,而加强了对再次缺血损伤的保护作用.丁苯酞能够增强这一效应.     

三七三醇皂苷对脑缺血大鼠脑室下区细胞增殖及星形胶质细胞的影响

目的:研究三七三醇皂苷(PTS)对局灶性脑缺血再灌注后脑室下区(SVZ)细胞增殖及星形胶质细胞的影响。方法:60只雄性SD大鼠随机分为假手术、生理盐水(NS)和PTS组,每组设再灌注3、7、14、21d亚组,每个时段各5只。采用改良的线栓法制备大脑右侧中动脉阻塞2h的大鼠短暂局灶性脑缺血模型,观察5-溴脱氧尿嘧啶和胶质纤维酸性蛋白(GFAP)在SVZ的表达情况。结果:再灌注后7d,PTS组与NS组SVZ细胞增殖水平达到峰值,至再灌注21d细胞增殖水平已明显回落,但仍高于正常水平;再灌注后7、14d,PTS组SVZ细胞增殖水平显著高于NS组。再灌注后3d,PTS组与NS组SVZ细胞GFAP表达达到峰值,至再灌注14d已恢复正常水平;再灌注后3、7d,PTS组SVZ的GFAP阳性细胞数显著高于NS组。结论:PTS可促进缺血再灌注后SVZ细胞的增殖水平,并上调GFAP的表达。     

环孢素A对戊四氮致痫过程中大鼠海马GFAP的干预研究

目的:研究环孢素A对戊四氮致痫过程中大鼠海马GFAP的影响,并观察大鼠癫痫发作行为变化.方法:72只大鼠随机分为空白对照组(N组)24只,非药物干预组(P组)24只和药物干预组24只(C组);P组和C组于每日给予腹腔注射戊四氮30mg/kg;同时C组每隔两日给予尾静脉注射环孢素A10mg/kg.采用免疫组化方法观察胶质原纤维酸性蛋白(GFAP)于4d、7d、14d的增生变化;同时观察各组大鼠癫痫发作的时间、发作级别和发作次数.结果:P组大鼠在4d、7d、14d各时间点均未出现癫痫发作时,已经出现胶质细胞增生,并且随着时间的增加胶质细胞增生的程度逐渐升高,与空白对照组(N)比较有显著性差异(P＜0.01);与C组比较有显著性差异(P＜0.01);C组大鼠在4d、7d、14d各时间点也均未出现癫痫发作,随着时间的增加胶质细胞增生的程度也逐渐升高,但胶质细胞增生的程度明显低于P组,与P组对应时间点比较,有显著性差异(P＜0.01);C组大鼠各时间点胶质细胞增生的程度与N组比较也有显著性差异(P＜0.05).结论:环孢素A干预后大鼠海马星形胶质细胞增生程度降低,减低了大鼠癫痫发作的级别和次数,延迟癫痫发作时间,因此环孢素A具有预防癫痫发作的作用.     

Increases in dopamine D3 receptor binding in rats receiving a cocaine challenge at various time points after cocaine self-administration: implications for cocaine-seeking behavior.

Previous research suggests that cocaine dysregulates dopamine D3 receptors. The present study examined the time course of changes in dopamine D3 receptor binding after terminating a cocaine self-administration regimen. [125I]-7-hydroxy-2-[N-propyl-N-(3'-iodo-2'-propenyl)-amino]-tetralin was used to label dopamine D3 receptors in rats that had undergone testing for cocaine-seeking behavior reinstated by a cocaine priming injection (15 mg/kg, i.p.; the behavior results have been previously published), and were killed 24 h after the test at time points that were either 2, 8, or 31-32 days after their last cocaine self-administration session. The results indicated a time-dependent increase in D3 receptor binding relative to controls that received saline yoked to the delivery of cocaine in an experimental animal. Specifically, there was no significant change in D3 receptor binding in cocaine-experienced rats killed at the 2- or 8-day time points relative to controls, but there was an increase in D3 receptor binding in the nucleus accumbens core and ventral caudate-putamen in rats killed at the 31- to 32-day time point. In a subsequent experiment, we replicated the increase in D3 receptor binding in rats that underwent a less extensive self-administration regimen, then were tested for cocaine-primed reinstatement of cocaine-seeking behavior, and then were killed 24 h later at a time point of 22 days after their last self-administration session. Furthermore, the increase in binding was attenuated by repeated 7-hydroxy-N,N-di-n-propyl-2-aminotetralin administration (1 mg/kg/day, s.c. for 14 days), a regimen that also reduces cocaine-seeking behavior in animals when tested in a nondrug state. Collectively, the findings suggest that regulatory responses of D3 receptors may be functionally related to changes in propensity for cocaine-seeking behavior.     

Chronic cerebral hypoperfusion-induced neuropathological changes in rats.

We investigated the time courses of histopathological changes in various brain regions following permanent occlusion of the bilateral common carotid arteries (2VO) in rats. 2VO rats exhibited rarefaction in the white matter, shrinkage of neurons in the cerebral cortex and hippocampus CA1-3 and dentate gyrus areas 1-3 days after the operation. These histological changes in the cortex and hippocampus were accompanied by a decrease in immunoreactivity for microtubule-associated protein 2 (MAP2), a marker protein of neuronal dendrites. Immunoreactivity for glial fibrillary acid protein (GFAP) was observed at 3-7 days after the 2VO operation. A marked increase in GFAP staining of the astrocytes in the cerebral cortex and hippocampus was found 30 days after ligation. Eight-arm radial maze performance was tested from 14 days to 60 days after the operation. The 2VO rats showed fewer initial correct responses than sham-operated control rats during a repeated training period. These findings suggested that the loss in dendritic MAP2 immunoreactivity and an increase in astroglial staining and/or rarefaction of the white matter may cause neuronal death, infarction and learning impairment under conditions of chronic hypoperfusion.     

Biochemical and immunohistological changes in the brain of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mouse.

We investigated neurochemically and neuropathologically the utility of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice as a model of Parkinson's disease. The changes in dopamine D1 and D2 receptors and dopamine uptake sites were determined by quantitative autoradiography using [3H]SCH23390, [3H]raclopride and [3H]mazindol, respectively. Dopamine and 3,4-dihydroxyphenyl acetic acid (DOPAC) contents in the striatum were measured by high-performance liquid chromatography. The distribution of nigral neurons and reactive astrocytes was determined by immunohistochemical staining with antibody against tyrosine hydroxylase (TH) and glial fibrillary acidic protein (GFAP). The mice received four intraperitoneal injections of MPTP (10 mg/kg) at 1-h intervals and then the brains were analyzed at 3 and 7 days after the treatments. No significant change in dopamine D1 receptors was observed in the striatum and substantia nigra after acute treatment with MPTP. Dopamine D2 receptors were reduced significantly in the substantia nigra only 7 days after the MPTP treatment, whereas striatum showed no significant change in the binding throughout the experiments. In contrast, dopamine uptake sites were reduced markedly in the striatum and substantia nigra 3 and 7 days after the MPTP treatment. Dopamine and DOPAC content were also reduced in the striatum 3 and 7 days after the MPTP treatment. An immunohistochemical study indicated a loss of the number of TH-positive neurons in the substantia nigra 7 days after the MPTP treatment. In contrast, numerous GFAP-positive astrocytes were evident in the striatum 7 days after the MPTP treatment. These results provide valuable information for the pathogenesis of acute stage of Parkinson's disease.     

Pathogenetic transition in the morphology of abnormal sperm in the testes and the caput, corpus, and cauda epididymides of male rats after treatment with 4,6-dinitro-o-cresol

In order to elucidate the pathogenesis of tailless sperm, 4,6-dinitro-o-cresol (DNOC) was administered to Jcl:SD male rats at daily oral doses of 0, 10 or 15mg/kg for 5 days. Sperm were collected from the caput, corpus, and cauda epididymides on days 1, 7 and 14 after the last dosing (D1, D7 and D14, respectively), counted and examined morphologically by phase-contrast and scanning electron microscopy. The incidence of abnormal sperm was significantly increased in the DNOC 15mg/kg group. On D1, peeled sperm (loss of mitochondrial sheath at the proximal end of the middle piece) was frequently observed in the caput epididymides, whereas sperm in the corpus and cauda epididymides had normal morphology. Distribution of the peeled sperm changed as time passed and the corpus epididymides showed a peak incidence on D7. On D14, the highest incidence of abnormal sperm was observed in the cauda epididymides, where the major abnormality was tailless. Similar effects were also found in the 10mg/kg group but were less potent. Transmission electron microscopy of testicular sperm on D1 revealed the presence of elongated spermatids that lacked the mitochondrial sheath at the proximal end of the middle piece, although the round and elongating spermatids looked normal. These results suggest that DNOC exposure of male rats primarily causes partial loss of the mitochondrial sheath in the testicular elongated spermatids, and that the affected sperm become tailless by D14 after reaching the cauda epididymides.     

Effect of chronic nicotine treatment and withdrawal on rat striatal D1 and D2 dopamine receptors.

The effects on rat striatal dopamine receptors after chronic nicotine administration (3 and 12 mg kg-1 day-1), and after withdrawal from chronic nicotine (12 mg kg-1 day-1), were studied. After 21 days of continuous minipump infusion, the control (saline) and nicotine-treated rats were killed. The nicotine-withdrawal rats were killed on day 28, 7 days after pump removal. Radioligand studies were performed to determine D1 ([3H]SCH23390) and D2 ([3H]spiperone) striatal dopamine receptor affinity (Kd) and maximum binding (Bmax). Dopamine inhibition of antagonist binding at 3 concentrations and the effect of 0.3 mM GTP on binding affinity were examined. No statistically significant differences between control and nicotine treatment or withdrawal groups were noted in either D1 or D2 receptor Kd or Bmax. Although nicotine has been shown to affect nigrostriatal dopamine release, chronic treatment does not appear to alter overall striatal dopaminergic receptor binding parameters.     

Physical dependence potential of an enkephalin analog, EK-399, in rats

The physical dependence potential of Tyr-D-Met(O)-Gly-EtPhe-NHNHCOCH3.AcOH (EK-399), a novel enkephalin analog with a potent analgesic effect, was assessed in rats. The animals were given EK-399 (0.008, 0.032, 0.125, or 0.5 mg/kg), morphine (0.125, 0.5, or 2 mg/kg), pethidine (2 or 8 mg/kg), or pentazocine (2 or 8 mg/kg) every hour through an implanted intravenous cannula. After 3 days of treatment, precipitated withdrawal tests were conducted: naloxone (5 mg/kg) was administered subcutaneously. Rats treated with morphine showed withdrawal signs such as hyperirritability, salivation, diarrhea, and weight loss. Rats treated with pethidine, pentazocine, or EK-399 showed similar signs, but they were less evident than those in morphine-treated rats. In abrupt withdrawal tests after 7 days of treatment, rats treated with morphine, pethidine, or pentazocine showed weight loss, whereas rats treated with EK-399 showed little or no weight loss. In substitution tests, EK-399 suppressed the withdrawal signs in morphine-dependent rats, and vice versa. These results show that EK-399 has a morphine-like physical dependence potential that is weaker than that of morphine, pethidine, or pentazocine in rats.     

Lorazepam 0.25 mg twice a day improves aspects of psychometric performance in healthy volunteers

The effects of lorazepam (0.25 mg) twice a day on several cognitive and performance tasks, pictures test, digit-symbol substitution test (DSST), choice reaction time (CRT) and critical flicker fusion (CFF), were investigated in healthy students. A double-blind independent group design was used to compare placebo and lorazepam (30 volunteers in each group). After randomisation, all subjects received placebo for 3 days (D), followed by 14 days of treatment, with either lorazepam or placebo. Subjects completed a battery of tests at Do, then D(3), D(7) , D(10) and D(14). D(3) performance was poorer in the lorazepam group except for CFF (ascending values and total values), yet the only significant improvement was in total reaction time on the CRT test. However, a significant improvement of performance was shown at D(7), D(10) and D(14) in the lorazepam group compared with the control group (except in recognition reaction time). The current study shows that low repeated doses of lorazepam are able to produce small improvements in some aspects of psychomotor and cognitive functions in healthy volunteers. Different points are discussed to explain the performance improvement: training effect, tolerance effect, partial inverse agonist effect and the possible release of cholecystokinin.     

瓜蒌薤白汤对肺纤维化模型肺泡灌洗液SOD、肺组织IL-10的影响

目的探讨瓜蒌薤白汤防治肺纤维化的作用及机制。方法用平阳霉素诱导肺纤维化模型大鼠后,用药组每天灌胃瓜蒌薤白汤,分别于第7、14天后处死各组大鼠,观察比较各组大鼠肺部病理组织学改变及肺泡灌洗液中超氧化物歧化酶(SOD)和肺组织中白细胞介素10(IL-10)的表达。结果第7、14天瓜蒌薤白汤组及正常对照组肺泡炎表达均显著低于模型组(P<0.05);第14天正常对照组、瓜蒌薤白汤组肺纤维化程度显著低于模型组;瓜蒌薤白汤组肺泡灌洗液中SOD活性、肺组织中IL-10的表达均高于模型对照组,但无统计学意义。结论瓜蒌薤白汤能明显减轻平阳霉素所致的大鼠肺泡炎及纤维化程度。     

Gentamicin Nephrotoxicity in Rat: Some Biochemical Correlates

Abstract: The present work examines the effect of treatment of rats with graded doses of the aminoglycoside antibiotic gentamicin on the concentration of reduced glutathione (GSH) and diamine oxidase (DAO) activity in the kidney, and DAO activity, creatinine and magnesium (Mg) in the plasma. The animals were given the antibiotic intramuscularly in doses of 20, 40, and 80 mg/kg/day for 6 days, and were killed 24 hr after the last injection. In another experiment rats were injected intramuscularly with gentamicin at a dose of 80 mg/kg/day for 6 days and were killed 1, 7 or 14 days after the last injection, and the above parameters were measured. Gentamicin reduced the body weights of rats in a dose-dependent manner. The weight reductions were most marked on days 4, 5 and 6 of the treatment. The body weights gradually recovered on withdrawing of the drug, and by day 14, they were not significantly different from those of the controls. Gentamicin produced significant and dose-dependent decreases in the renal concentration of GSH. Seven and 14 days after withdrawing the drug, the GSH concentrations were still significantly below that of the controls. Plasma Mg concentrations were significantly decreased, and plasma creatinine concentrations significantly increased by gentamicin. These effects persisted 7 and 14 days after cessation of treatment. Plasma DAO activity was not detectable in the control or gentamicin-treated rats. In the renal cortex, the activity of the enzyme, measured 1, 7 and 14 days after the treatment, was not significantly different from that of the control. Histopathologically, the drug produced dose-dependent proximal renal tubular necrosis. Seven days after withdrawal of gentamicin, the degree of necrosis was less marked, and 14 days after drug withdrawal, renal histology was apparently normal.